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Role of Interleukin-22 in the Salivary Gland Disorder in Autoimmune Sj?gren's Syndrome

Award Number: R03AI142273
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/11/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2022

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Role of Interleukin-22 in the Salivary Gland Disorder in Autoimmune Sj?gren's Syndrome - Project Summary Sjӧgren’s syndrome (SS) is a chronic autoimmune disease that inflicts damage and dysfunction to salivary and lacrimal glands and many other organs, resulting in dry mouth, dry eyes and various systemic health problems. SS affects the oral and systemic health and life quality of 2-4 million Americans, with no cure or effective biological therapies currently available. An urgent need in SS research is to better understand the causes and pathogenic processes of this highly complex and multi-factorial disease, and to identify critical new therapeutic targets for the development of effective and targeted therapies for this high-impact autoimmune disease. The goal of this project is to define the previously unexplored role of cytokine interleukin-22 (IL-22) in vivo in the pathogenic development of salivary gland disorder in SS. Our preliminary studies have generated strong evidence that excessive IL-22, a cytokine with well-documented epithelial tissue-protective function, can cause salivary gland tissue damage and secretory hypofunction in both normal and SS-prone mice. In this proposed study, we will test the central hypothesize that in SS disease, endogenously produced IL-22 critically contributes to the pathological changes and secretory dysfunction of the salivary glands. We will test this hypothesis in two mouse models of human SS disease. In Aim 1 of the study, we will determine the in vivo function of endogenous IL-22 in the development of salivary gland pathologies and dysfunction through antibody-mediated neutralization of IL-22 in the non-obese diabetic mouse, a spontaneous SS disease model. In Aim 2, we will define the role of endogenous IL-22 in SS by using IL-22 gene-deficient mice and an autoantigen-induced SS disease model. In both aims, we will examine how the ablation of endogenous IL-22 activity affects the development of SS-like salivary gland disorder by assessing the damage, inflammation, salivary secretion and molecular changes of salivary gland tissues. Successful completion of this study will for the first time define the salivary gland- and SS disease-specific role of IL-22. It will also pave the foundation for further investigation and elucidation of the biology, functional specificity and plasticity, and therapeutic potential of IL-22 in SS disease and various other epithelial tissue autoimmune inflammatory disorders.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	7/26/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $99,500 )
2020	2020	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	5/8/2020	NON-COMPETING CONTINUATION	$99,500
														Subtotal = $99,500

Issue Date FY: 2019 ( Subtotal = $99,500 )
2019	2019	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	6/11/2019	NEW	$99,500
														Subtotal = $99,500

Grand Total All Awards = $199,000

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Role of Interleukin-22 in the Salivary Gland Disorder in Autoimmune Sj?gren's Syndrome

Award Number: R03AI142273

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/11/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2022

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